Molecular descriptors in chemoinformatics, computational combinatorial chemistry, and virtual screening

Many contemporary applications in computer-aided drug discovery and chemoin formatics depend on representations of molecules by descriptors that captur e their structural characteristics and properties. Such applications includ e, among others, diversity analysis, library design, and virtual screening. Hundreds of molecular descriptors have been reported in the literature, ra nging from simple bulk properties to elaborate three-dimensional formulatio ns and complex molecular fingerprints, which sometimes consist of thousands of bit positions. Knowledge-based selection of descriptors that are suitab le for specific applications is an important task in chemoinformatics resea rch. If descriptors are to be selected on rational grounds, rather than gue sses or chemical intuition, detailed evaluation of their performance is req uired. A number of studies have been reported that investigate the performa nce of molecular descriptors in specific applications and/or introduce nove l types of descriptors. Progress made in this area is reviewed here in the context of other computational developments in combinatorial chemistry and compound screening.